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Hyperosmolar hyperglycemic state (HHS), also known as hyperosmolar non-ketotic state (HONK), is a complication of
diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
in which high blood sugar results in high
osmolarity Osmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/ ...
without significant
ketoacidosis Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes i ...
. Symptoms include signs of
dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...
, weakness, leg cramps,
vision problems Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...
, and an
altered level of consciousness An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousn ...
. Onset is typically over days to weeks. Complications may include
seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
s, disseminated intravascular coagulopathy, mesenteric artery occlusion, or
rhabdomyolysis Rhabdomyolysis (shortened as rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some o ...
. The main risk factor is a history of
diabetes mellitus type 2 Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...
. Occasionally it may occur in those without a prior history of diabetes or those with
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...
. Triggers include
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
s,
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, trauma, certain medications, and
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
s. Diagnosis is based on
blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...
s finding a blood sugar greater than 30 mmol/L (600 mg/dL), osmolarity greater than 320 mOsm/kg, and a pH above 7.3. Initial treatment generally consists of
intravenous fluid Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
s to manage dehydration, intravenous
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
in those with significant
ketones In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
,
low molecular weight heparin Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of Thrombosis prevention, blood clots and, in the treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism), and ...
to decrease the risk of
blood clot A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
ting, and
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s among those in whom there are concerns of infection. The goal is a slow decline in blood sugar levels.
Potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...
replacement is often required as the metabolic problems are corrected. Efforts to prevent
diabetic foot ulcer Diabetic foot ulcer is a breakdown of the skin and sometimes deeper tissues of the foot that leads to sore formation. It is thought to occur due to abnormal pressure or mechanical stress chronically applied to the foot, usually with concomitant pre ...
s are also important. It typically takes a few days for the person to return to baseline. While the exact frequency of the condition is unknown, it is relatively common. Older people are most commonly affected. The risk of death among those affected is about 15%. It was first described in the 1880s.


Signs and symptoms

Symptoms of high blood sugar including increased thirst (polydipsia), increased volume of urination (polyuria), and increased hunger (
polyphagia Polyphagia, or hyperphagia, is an abnormally strong, wikt:incessant, incessant sensation of Hunger (physiology), hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not s ...
). Symptoms of HHS include: * Altered level of consciousness * Neurologic signs including: blurred vision, headaches, focal seizures, myoclonic jerking, reversible paralysis * Motor abnormalities including flaccidity, depressed reflexes, tremors or fasciculations *
Hyperviscosity Hyperviscosity syndrome is a group of symptoms triggered by an increase in the viscosity of the blood. Symptoms of high blood viscosity include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic symp ...
and increased risk of blood clot formation * Dehydration * Weight loss * Nausea, vomiting, and abdominal pain * Weakness *
Low blood pressure with standing Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...


Cause

The main risk factor is a history of
diabetes mellitus type 2 Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...
. Occasionally it may occur in those without a prior history of diabetes or those with
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...
. Triggers include
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
s,
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, trauma, certain medications, and
heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
s. Other risk factors: * Lack of sufficient insulin (but enough to prevent ketosis) * Poor kidney function * Poor fluid intake (dehydration) * Older age (50–70 years) * Certain medical conditions ( cerebral vascular injury,
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
) * Certain medications (
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
s,
beta-blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention) ...
s, thiazide diuretics,
calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
s, and
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...
)


Pathophysiology

HHS is usually precipitated by an infection,
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
,
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
or another acute illness. A relative insulin deficiency leads to a serum
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
that is usually higher than 33 mmol/L (600 mg/dL), and a resulting serum
osmolarity Osmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/ ...
that is greater than 320 mOsm. This leads to excessive urination (more specifically an osmotic diuresis), which, in turn, leads to volume depletion and hemoconcentration that causes a further increase in blood glucose level.
Ketosis Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability. In physiological ketosis, ketones in the blood are elevated above bas ...
is absent because the presence of some
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
inhibits hormone-sensitive lipase-mediated fat tissue breakdown.


Diagnosis


Criteria

According to the
American Diabetes Association The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes, including type 1 diabetes ...
, diagnostic features include: * Plasma glucose level >30 mmol/L (>600 mg/dL) * Serum osmolality >320 mOsm/kg * Profound dehydration, up to an average of 9L (and therefore substantial thirst (
polydipsia Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives , which is derived . Polydipsia is a nonspecific symptom in v ...
)) * Serum pH >7.30 * Bicarbonate >15 mEq/L * Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L) * Some alteration in consciousness * BUN > 30 mg/dL (increased) * Creatinine > 1.5 mg/dL (increased)


Imaging

Cranial imaging is not used for diagnosis of this condition. However, if an
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.


Differential diagnosis

The major differential diagnosis is
diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening acute complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally ...
(DKA). In contrast to DKA, serum glucose levels in HHS are extremely high, usually greater than 40-50 mmol/L (600 mg/dL).
Metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidn ...
is absent or mild. A temporary state of confusion (delirium) is also more common in HHS than DKA. HHS also tends to affect older people more. DKA may have fruity breath, and rapid and deep breathing. DKA often has serum glucose level greater than 300 mg/dL (HHS is >600 mg/dL). DKA usually occurs in type 1 diabetics whereas HHS is more common in type 2 diabetics. DKA is characterized by a rapid onset, and HHS occurs gradually over a few days. DKA also is characterized by ketosis due to the breakdown of fat for energy. Both DKA and HHS may show symptoms of dehydration, increased thirst, increased urination, increased hunger, weight loss, nausea, vomiting, abdominal pain, blurred vision, headaches, weakness, and low blood pressure with standing.


Management


Phases and timelines

Th
JBDS
HHS care pathway comprises 3 main themes to consider when managing a patient with HHS: * clinical assessment and monitoring * interventions * assessments and prevention of harm To streamline management, there are 5 phases of therapy from the time of recognition of the condition to resolution: # 0–60 min # 1–6 hours # 6–12 hours # 12–24 hours # 24–72 hours


Intravenous fluids

Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of
normal saline Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By intravenous therapy, inje ...
often in the range of 1 L/h for the first few hours or until the condition stabilizes.


Electrolyte replacement

Potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...
replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output.


Insulin

Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/L, then an insulin infusion of 0.1 units/kg/hr is started. The goal for resolution is a blood glucose of less than 200 mg/dL.


References


External links

{{Diabetes Medical emergencies Complications of diabetes Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate